Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer

Abstract

Background: Combined analysis from two randomized phase 3 trials showed afatinib improved overall survival (OS) compared with platinum doublets in patients with Exon 19 deletion (Del‐19) mutation. However, in patients with Leu858Arg (L858R) point mutation, afatinib efficacy did not differ significantly from chemotherapy. We hypothesized that this discrepancy was due to differential efficacy of cisplatin plus pemetrexed between Del‐19 and L858R. Methods: This study is a multicenter retrospective study. We reviewed medical records of patients who had received cisplatin plus pemetrexed as first line chemotherapy. Efficacies were evaluated among epidermal growth factor receptor (EGFR) mutation status: Del‐19; L858R; and wild type. Results: Among 304 patients, 78 (25.7%) harbored EGFR mutations: Del‐19 (36/78 patients, 46.2%); and L858R (42/78, 53.8%). Median PFS of L858R group (9.4 months, 95% confidence interval [CI]: 7.0‐12.6) was significantly longer than Del‐19 group (5.5 months, 95% CI: 3.6‐8.6) (p = 0.049). Response rate (RR) and OS presented no significant difference among L858R, Del‐19 or wild type. In multivariate analysis, EGFR mutation status (L858R versus Del‐19) was the only significant factor for longer PFS (Hazard ratio [HR]: 0.78, 95% CI: 0.62‐0.98) (p = 0.033). Conclusions: Our study indicated better efficacy of cisplatin plus pemetrexed in L858R than in Del‐19 patients. This result could be a valuable suggestion to consider better therapeutic strategies for L858R patients.